Dopaminergic neurons—Alteration in the kinetic properties of tyrosine hydroxylase after cessation of impulse flow

Morgenroth, Victor H.; Walters, Judith R.; Roth, Robert H.

doi:10.1016/0006-2952(76)90240-9

Cited by 93 publications

(26 citation statements)

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“…Early on it was hypothesized that a reduction in neuronal output may result in decreased neuronal release of dopamine. Therefore, the observed increase in dopamine synthesis and intracellular content following acute GHB exposure could be due to compensatory processes responding to the reduction of extracellular dopamine levels (Roth and Suhr, 1970;Morgenroth et al, 1976). The present in vivo microdialysis studies clearly show that acute, systemic administration causes a reduction in basal dopamine release.…”

Section: Discussionmentioning

confidence: 51%

“…Several researchers have shown that acute GHB administration results in a suppression of dopaminergic neuronal jpet.aspetjournals.org activity and an increase in intracellular dopamine content, in addition to its behavioral effects (Roth and Suhr, 1970;Morgenroth et al, 1976;Roth et al, 1980). Early on it was hypothesized that a reduction in neuronal output may result in decreased neuronal release of dopamine.…”

Section: Discussionmentioning

confidence: 99%

“…Roth et al (1980) discovered that GHB administration to rats resulted in an inhibition of striatal dopaminergic neuronal firing and possibly reduced release. This inhibition of activity and release is accompanied by increased dopamine biosynthesis and decreased catabolism (Roth and Suhr, 1970;Morgenroth et al, 1976;Nowycky and Roth, 1979;Roth et al, 1980). This compensatory mechanism is probably driven by a decrease in the available pool of extracellular dopamine (DA) that can interact with the presynaptic autoreceptors responsible for regulating synthesis.…”

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confidence: 99%

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Pharmacokinetics and Pharmacodynamics of γ-Hydroxybutyric Acid during Tolerance in Rats: Effects on Extracellular Dopamine

Raybon

Boje²

2006

J Pharmacol Exp Ther

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␥-Hydroxybutyrate (GHB) is a potent sedative/hypnotic and drug of abuse. Tolerance develops to GHB's sedative/hypnotic effects. It is hypothesized that GHB tolerance may be mediated by alterations in central nervous system pharmacokinetics or neurotransmitter response. Rats were dosed daily with GHB (548 mg/kg s.c. q.d. for 5 days), and sleep time was measured as an index of behavioral tolerance. Plasma and brain GHB pharmacokinetics on days 1 and 5 were monitored using blood and microdialysis sampling. Extracellular (ECF) striatal dopamine levels were measured by microdialysis as a pharmacodynamic endpoint of tolerance. Pharmacokinetic (PK)/pharmacodynamic (PD) modeling was performed to describe the plasma and brain disposition using an indirect response model with inhibition of dopamine synthesis rate to describe the pharmacodynamic response. GHB plasma and brain ECF concentration versus time profiles following acute or chronic exposure were not significantly different. GHB sedative/hypnotic tolerance was observed by day 5. Acute GHB administration resulted in a decrease in striatal ECF dopamine (DA) levels compared with baseline levels. GHB tolerance was reflected by a 60% decrease in dopamine area under the curve (effect and baseline): acute, 10.1 Ϯ 15.3% basal DA/min/10 Ϫ3 versus chronic, 4.73 Ϯ 1.49% basal DA/min/10 Ϫ3 (p Ͻ 0.05, n ϭ 5; unpaired Student's t test). The PK/PD model revealed an increase in the IC50 following chronic exposure indicating decreased dopaminergic sensitivity toward the inhibitory effects of GHB. Our findings indicate that GHB pharmacokinetics do not contribute to behavioral tolerance; however, changes in neurotransmitter responsiveness may suggest specific neurochemical pathways involved in the development and expression of tolerance.

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Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of γ-Hydroxybutyric Acid during Tolerance in Rats: Effects on Extracellular Dopamine

Raybon

Boje²

2006

J Pharmacol Exp Ther

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“…The common feature of all these experimental paradigms was an electrophysiological activation of the relevant DA system. However, tyrosine effects on striatal DOPA accumulation have also been noted in rats treated with gamma-butyrolactone (Sved and Fernstrom 1981), a drug which reduces nigrostriatal impulse flow but activates striatal TH (Walters and Roth 1974;Morgenroth et al 1976). Thus it is probably not increased DA neuronal activity per se but the resultant activation of TH that is critical to the induction of precursor dependence (Sved and Fernstrom 1981).…”

Section: Discussionmentioning

confidence: 99%

“…The availability of tyrosine in the brain normally exceeds the capacity of the enzyme tyrosine hydroxylase (TH) to convert it to DOPA (Carlsson and Lindqvist 1978;Morgenroth et al 1976;Joh et al 1978). Since the conversion of DOPA to DA is rapid and efficient, DA synthesis usually depends on TH activity and not on tyrosine levels (Wurtman et al 1974;Carlsson and Lindqvist 1978).…”

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confidence: 99%

Tyrosine Augments Acute Clozapine- but not Haloperidol-Induced Dopamine Release in the Medial Prefrontal Cortex of the Rat An in vivo Microdialysis Study

Jaskiw

Collins

Pehek

et al. 2001

Neuropsychopharmacology

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Tyrosine availability can influence dopamine (DA) synthesis in highly electrophysiologically active DAergic neurons, such as those innervating the medial prefrontal cortex (MPFC).In most brain dopamine (DA) systems, levels of the DA precursor tyrosine do not significantly affect dopaminergic transmission. The availability of tyrosine in the brain normally exceeds the capacity of the enzyme tyrosine hydroxylase (TH) to convert it to DOPA (Carlsson and Lindqvist 1978;Morgenroth et al. 1976;Joh et al. 1978). Since the conversion of DOPA to DA is rapid and efficient, DA synthesis usually depends on TH activity and not on tyrosine levels (Wurtman et al. 1974;Carlsson and Lindqvist 1978). However, precursor dependence of DA synthesis has been demonstrated in the light-activated retina (Fernstrom et al. 1984(Fernstrom et al. , 1986 as well as in striatal DA neurons after administration of haloperidol, spiperone, reserpine or amfonelic acid (Scally et al. 1977;Sved et al. 1979;Fuller and Snoddy 1982) or after marked DA depletion (Melamed et al. 1980). The common feature of these paradigms is a marked increase in the electrophysiological activity of the relevant DA system. Such data suggest that precursor dependence of DA synthesis may be a latent property of all DA neurons, but one which emerges only under conditions of increased dopaminergic activity. (Chiodo et al. 1984;White and Wang 1984), precursor dependence of medial prefrontal cortical (MPFC) DA synthesis might be expected even under basal conditions. Even within the MPFC, however, tight feedback systems limit the ability of exogenous tyrosine administration to augment DA synthesis (Tam et al. 1990). Intriguingly, in rats pretreated with FG-7142, a beta-carboline known to preferentially increase MPFC synthesis, utilization and release Roth 1985, 1990;Bradberry et al. 1991), administration of tyrosine robustly enhances MPFC DA synthesis (Tam et al. 1990). We postulated that such precursor dependence would also be established by other drugs which activate mesocortical dopaminergic activity.The atypical and clinically superior antipsychotic drug, clozapine, has already been demonstrated to preferentially release DA in the prefrontal cortex of the rat (Moghaddam and Bunney 1990; Pehek and Yamamoto 1994;Yamamoto and Cooperman 1995) as well as of the non-human primate (Youngren et al. 1999) and to preferentially activate DA neurons projecting to cortical regions (White and Wang 1983;Goldstein et al. 1993). Accordingly, we postulated that the co-administration of tyrosine and clozapine would potentiate MPFC DA synthesis. We further postulated that if the increased DA synthesis were reflected in increased DA release, then administration of tyrosine to clozapine-pretreated rats would augment MPFC DA levels as measured by in vivo microdialysis. Finally, since haloperidol, but not clozapine, preferentially activates nigrostriatal DA synthesis and release, we anticipated that tyrosine would enhance dialysate DA concentrations in the striatum but not the MPFC of haloperi...

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Effects of a Dopamine Agonist Piribedil in Depressed Patients

Post¹

1978

Arch Gen Psychiatry

162

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Dopaminergic neurons—Alteration in the kinetic properties of tyrosine hydroxylase after cessation of impulse flow

Cited by 93 publications

References 15 publications

Pharmacokinetics and Pharmacodynamics of γ-Hydroxybutyric Acid during Tolerance in Rats: Effects on Extracellular Dopamine

Pharmacokinetics and Pharmacodynamics of γ-Hydroxybutyric Acid during Tolerance in Rats: Effects on Extracellular Dopamine

Tyrosine Augments Acute Clozapine- but not Haloperidol-Induced Dopamine Release in the Medial Prefrontal Cortex of the Rat An in vivo Microdialysis Study

Effects of a Dopamine Agonist Piribedil in Depressed Patients

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